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Biomedical subjects

N Okamura

Publications and source records attributed to N Okamura.

At least 109 records · Page 6Linked to original sources
PubMed1994

Effect of a peptide from Panax ginseng on the proliferation of baby hamster kidney-21 cells.

An alkaline fraction separated by ion exchange chromatographies from the water extract of Panax ginseng root stimulated the proliferation of baby hamster kidney-21 cells. Separation of the alkaline fraction by MCI-gel CHP 20P column chromatography followed by dialysis provided an active material. By a reversed-phase HPLC the active material was separated into six fractions, and an active colorless compound 1 was obtained from fraction 2 in a pure state. Compound 1 was composed of the following amino acids; Gly, Arg, Glu, Val in a ratio of 1:1:1:1, and caused 20% enhancement of proliferation of BHK-21 cells at a concentration of 3.40 microM. On the basis of physical and spectral data the structure of compound 1 was established as a tetrapeptide, Gly-Arg-gamma-Glu-Val-NH2.

Amino Acid Sequence↗
PubMed1994

Effects of tanshinone VI derivatives on post-hypoxic contractile dysfunction of perfused rat hearts.

The present study was undertaken to elucidate the effects of sodium tanshinone VI 1-phenolate (1), 1'-O-hydrogen succinyltanshinone VI 1-O-hydrogen succinate (2), and disodium 1'-O-succinyltanshinone VI 1-O-succinate (3), water-soluble derivatives of tanshinone VI, on post-hypoxic contractile recovery of isolated perfused rat hearts. The effects were compared with those of tanshinone VI as tested previously. The hearts were perfused for 20 min under hypoxic conditions, followed by 45 min reoxygenation, and their cardiac performance was determined. Changes in tissue sodium, potassium, calcium, and magnesium contents after reoxygenation, and release of creatine kinase and purines and bases (ATP metabolites) during hypoxia/reoxygenation were also examined. The derivatives were dissolved in a Krebs-Henseleit buffer and administered at concentrations of 42 nM into the buffer. Hypoxia/reoxygenation resulted in slight recovery of cardiac contractile force, significant alterations in tissue ion concentrations, and pronounced release of creatine kinase and ATP metabolites, suggesting hypoxia/reoxygenation-induced functional and morphological damage. The tanshinone VI derivatives improved post-hypoxic contractile recovery, which was associated with restoration of tissue ionic concentrations, and diminishment of the release of creatine kinase and ATP metabolites from the hypoxic/reoxygenated hearts. The efficacy of these compounds was similar to that of tanshinone VI. The results suggest that water-soluble tanshinone VI derivatives, like tanshinone VI itself, are beneficial for hypoxia/reoxygenation injury.

Adenosine Triphosphate↗
PubMed1994

Protective effect of ginseng saponins against impaired brain growth in neonatal rats exposed to ethanol.

This study was performed to determine the active constituents of the root of Panax ginseng C. A. Mayer in the amelioration of ethanol-induced impediment of brain growth in the neonatal stage. To establish an animal model of the brain growth impediment caused by ethanol, ethanol (6 g/kg s.c.) was administered to rat pups on postnatal day 6, which corresponded to the third trimester of pregnancy for humans. Brain weight, especially cerebellar weight, was significantly reduced in the ethanol-exposed pups. In contrast, neither separation from dams nor pentobarbital treatment affected brain weight. A saponin fraction of ginseng extract prevented this ethanol-induced reduction of brain weight. Some ginseng saponins including ginsenosides Rg1, Rb2, Rd, Rf and Re effected stimulated a potent recovery of cerebellum growth in this animal model.

Animals↗
PubMed1994

[The factors involved in invasive ability of endometrial carcinoma cells].

The in vitro invasive ability, the expression of cell adhesion molecule E-cadherin, activity of matrix metalloproteinase (MMP) and K-ras point mutation were investigated in eight human endometrial carcinoma cell lines. 1) In vitro invasive abilities of endometrial carcinoma cell lines depend on the degree of cell differentiation and the origin of cell lines. A poorly-differentiated carcinoma cell line (NUE-1) and a cell line derived from metastatic lymph node (SNG-M) were more invasive than moderately-(HEC-1A, HEC-1BE) and well-differentiated (HEC-6, Ishikawa) cell lines. 2) Immunohistochemically, less or non-invasive cell lines expressed E-cadherin strongly, whereas a highly invasive cell line (NUE-1) expressed E-cadherin weakly. 3) When cultured on Matrigel-coated dishes, the tumor cells derived from moderately- and well-differentiated carcinoma aggregated with each other and did not invade Matrigel in the invasion assay. The aggregated cells expressed E-cadherin more strongly when cultured on Matrigel. 4) 72-kD gelatinase (MMP-2) was secreted in serum-free conditioned medium of all cell lines. In an invasive cell line (NUE-1,SNG-M), the activity of MMP-2 was stronger than in other cell lines. And the activity of 92-kDa gelatinase (MMP-9) was detected in most invasive cell line (NUE-1). 5) Point mutation of K-ras codon 12 was detected in four of eight (50%) cell lines by the PCR-RFLP method. The changes in the DNA sequence were identified, but K-ras point mutation was not correlated with in vitro invasiveness of the tumor cells.

Cadherins↗
PubMed1994

[Management of the uterine endometrial cancer cases whose cytological and histologic specimens cannot be obtained from the uterine cavity--assessment by CA125 or vaginal ultrasonography].

An examination for endometrial cancer has been done by cytology. However, cytology is sometimes not possible because of closed or narrow cervix of postmenopausal woman. We did a retrospective study regarding the usefulness of CA125 or transvaginal ultrasonography in postmenopausal cases. The mean +/- S.D. of CA125 in normal menopausal women was 10.3 +/- 3.0 U/ml. The value of mean +/- 2S.D., the finding of Relative Operating Characteristic curve and the purpose that false positive was 0%, so we set 17 U/ml as the cut off value for CA125. In 46 cases with postmenopausal endometrial carcinoma, 23 cases were screened; and in 30 cases with surgical stage I, 10 cases were screened with this cut off value. The echoic patterns for uterine cavities which were observed by transvaginal ultrasonography were divided into 4 patterns (type I: anechoic pattern, type II: linear pattern, type III: clear mass pattern, type IV: unclear mass pattern). In 20 cases with postmenopausal endometrial cancer, 19 cases had type III or IV. In 41 normal postmenopausal women, 26 cases showed an anechoic pattern and 14 cases showed a linear pattern. It was found that 97.5% of cases with anechoic or linear patterns were normal endometrium. The screening by transvaginal ultrasonography was more useful than CA125. However CA125 was more useful than transvaginal ultrasonography in detecting lymph node metastasis.

Aged↗
PubMed1994

[Usefulness of CA125 determination in the diagnosis of lymph node metastasis in post menopausal uterine endometrial carcinoma].

It has been difficult to diagnose all but advanced cases of lymph node metastases with CT or MRI. It has been reported that the serum value of CA125 rises with the stage of endometrial cancer. This level is lower in the postmenopausal period than before menopause. In this study, we have examined the usefulness of CA125 for the assessment of lymph node metastasis in 43 postmenopausal endometrial cancer cases. There were significant differences in the CA125 level between lymph node metastasis positive cases and negative cases, between cancers occupying > or = 1/2 and < 1/2 of the uterine cavity, between lesions of > or = 1/3 and < 1/3 depth, and between surgical stages I, and III and IV. There was no significant correlation between serum CA125 levels and histological type. The serum CA125 value (mean +/- S.D., U/ml) was 179.0 +/- 291.0 (N = 6) in cases with lymph node metastasis and 15.8 +/- 8.5 (N = 37) in cases without metastasis (p < 0.001). We concluded that 32U/ml, which equals the mean + 2S.D., is a useful cut off value for suspicion of lymph node metastasis. The sensitivity and specificity of this cut off value were 100 (6/6) and 91.9% (34/37), respectively. This standard seems likely to considerably increase the accuracy of diagnosis of lymph node metastasis when taken in combination with the several factors already known to predict this. It may also be useful to diagnose lymph node metastasis in the preoperative period. Although the number of cases in this study was small, the data seem very promising for planning therapy for individual cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Forskolin stimulates porcine sperm capacitation by increasing calcium uptake.

Using the fluorescent calcium indicator fura-2, forskolin was found to dose-dependently cause an immediate increase in the concentration of intracellular free calcium of porcine cauda epididymal sperm. This stimulatory effect of forskolin is due to the enhancement of Ca2+ uptake by the verapamil-sensitive transporter on the sperm plasma membrane and results in the promotion of the sperm capacitation and subsequent acrosome reaction.

Acrosome↗
PubMed1993

Cytosolic protein phosphatase may turn off activated NADPH oxidase in guinea pig neutrophils.

Protein phosphatase inhibitors, okadaic acid and calyculin A, potentiated and elongated N-formyl-methionyl-leucyl-phenylalanine-induced superoxide anion (O2-) production in guinea pig neutrophils. The activity of NADPH oxidase in the membrane fraction prepared from phorbol 12-myristate 13-acetate-stimulated neutrophils was inactivated by the addition of the cytosol from resting neutrophils, such inactivation of NADPH oxidase was also suppressed by the protein phosphatase inhibitors. We previously reported that phosphorylation of the 46-kDa protein by protein kinase C is one of the activation mechanisms of NADPH oxidase-dependent superoxide anion production. In the cytosol fraction, we found protein phosphatase activity that catalyzed dephosphorylation of 32P-labeled phosphoproteins including the 46-kDa protein. Dephosphorylation of the 46-kDa protein was inhibited by the addition of okadaic acid and calyculin A. These results indicate that dephosphorylation of the 46-kDa protein by protein phosphatase is involved in the inactivation of NADPH oxidase. NADPH oxidase activity in guinea pig neutrophil may be regulated by the phosphorylation/dephosphorylation state of the 46-kDa protein by protein kinase C and protein phosphatase.

Animals↗
PubMed1993

Enhanced liver regeneration in rats treated with 15-deoxyspergualin alone and in combination with FK 506.

The effects of 15-deoxyspergualin (DSG) alone and in combination with FK 506 (FK) on liver regeneration after 2/3 hepatectomy was studied. The administration of 5 mg/kg DSG increased the liver weight as a percentage of the body weight (RLW) in the 5 days following the hepatectomy. This enhanced regeneration was not affected if interleukin(IL)-2 was also given. The combination of 1 mg/kg DSG and 0.05 mg/kg FK induced the highest values for RLW. The amounts of food and water intake increased in the DSG and FK combined group. Blood chemistry indicated that the combined administration of DSG and FK could reduce side-effects more effectively than separate administration. These observation led us to conclude that DSG has a stimulating potency in liver regeneration by means of direct suppression of T cell activation, and there is a synergistic effect on regeneration by DSG and FK.

Animals↗
PubMed1993

Effect of thiol compounds on in vitro development and intracellular glutathione content of bovine embryos.

The purpose of this investigation was to determine the effect of beta-mercaptoethanol (beta-ME) and cysteamine, low-molecular-weight thiol compounds, on the development and intracellular glutathione content of bovine embryos obtained by in vitro fertilization of in vitro-matured oocytes. Embryos developed to the 6-8-cell stage after in vitro fertilization were cultured without feeder cells in TCM-199 containing 10% fetal calf serum with or without beta-ME or cysteamine. The percentage of embryos that developed to the blastocyst and hatched blastocyst stages were significantly higher in medium containing beta-ME or cysteamine. Also, total intracellular glutathione levels were higher for embryos cultured in the medium with beta-ME or cysteamine than for those cultured in medium without thiol compounds. Moreover, when buthionine sulfoximine, a specific inhibitor of glutathione synthesis, was added to medium containing thiol compounds, there was a reduction both in the development of embryos to the blastocyst stage and in intracellular glutathione content. These results indicate that the inclusion of low-molecular-weight thiol compounds aids the in vitro development of bovine embryos without feeder cells and that the effect of thiol compounds is mediated through the increase of intracellular glutathione levels.

Animals↗
PubMed1993

Chemical analysis of lipopolysaccharides of Shigella sonnei form II strains expressed by cloned form I antigen genes.

A compositional sugar analysis was carried out on lipopolysaccharide (LPS) from Shigella sonnei form II in which a plasmid with cloned form I antigen genes had been introduced. The recipient form II strains contained galactose, glucose, heptose, glucosamine, and 2-keto-3-deoxyoctonic acid (KDO) (2: 3: 1: 2: 2) in its LPS, while the transformant form I LPS contained, besides these sugars, N-acetyl-L-altrosaminouronic acid as an additional sugar constituent, which is known to be one of the antigenic determinants of form I antigen.

Cloning, Molecular↗
PubMed1993

[Characteristics of the Shigella flexneri strains isolated from Japanese monkeys (Macaca fuscata)].

Shigella flexneri was isolated from 11 of 95 Japanese monkeys (Macaca fuscata) purchased by the Animal Research Center, Tokyo Medical and Dental University, during the period from 1988 through 1990. The serotypes of the isolates were 4a (5 isolates), 2a (4 isolates), 2b (1 isolate), and varY (1 isolate). Although some of the strains in the same serotypes were similar, others were different in their antibiotic susceptibility patterns or the plasmid profiles. Our results suggested that various types of Shigella flexneri had infected the Japanese monkeys. However, the source(s) and the routes of infection were unclear. Dysentery in the Japanese monkey has not yet been reported. So, to our knowledge, this may be the first report of dysentery among Japanese monkeys.

Animals↗
PubMed1993

Reduced susceptibilities of Shigella sonnei strains isolated from patients with dysentery to fluoroquinolones.

Seven clinical isolates of Shigella sonnei with reduced susceptibilities to fluoroquinolones (sparfloxacin, ciprofloxacin, and ofloxacin) were obtained. The MICs of fluoroquinolones against these S. sonnei strains were 16 to 32 times higher than those obtained against typical strains that are highly susceptible to these agents. The kinetics of [14C]ofloxacin accumulation in these clinical strains were not different from those in the fully susceptible strains. However, DNA synthesis was much less inhibited by ofloxacin in the strains with reduced susceptibility. Analysis of the in vitro activity of the partially purified DNA gyrase from these isolates showed that the decreased quinolone susceptibility of the S. sonnei strains was likely due to mutation of the DNA gyrase subunit A gene.

Anti-Infective Agents↗
PubMed1993

Digoxin-cyclosporin A interaction: modulation of the multidrug transporter P-glycoprotein in the kidney.

The mechanism of a renal tubular digoxin-cyclosporin A interaction was elucidated using a kidney epithelial cell line and the isolated perfused rat kidney. The cells expressed an excess amount of human P-glycoprotein on the apical membranes by transfection with MDR1 cDNA. Cyclosporin A inhibited the transepithelial transport of digoxin mediated by human P-glycoprotein; net basal-to-apical transport across the cell monolayer was 22.8, 21.2, 6.61 and 0.91 pmol/mg of protein/3 hr in the presence of 0, 1, 5 and 10 microM cyclosporin A, respectively. Cyclosporin A also reduced the renal tubular secretion of digoxin by the kidney. The ratio of fractional excretion/filtration fraction for digoxin was 2.88 +/- 0.71 (mean +/- S.D.) in the control, and this was decreased to 1.21 +/- 0.09 and 1.05 +/- 0.13 in the presence of 1 and 5 microM cyclosporin A, respectively. Because no signs of acute nephrotoxicity were observed, a direct effect of cyclosporin A accounted for the reduced secretion. On the other hand, digoxin did not affect cyclosporin A transport by P-glycoprotein. These findings indicate that serum concentrations of digoxin in patients should be carefully monitored when administered concurrently with cyclosporin A. The present transepithelial transport system using the transfectant cells is a simple and useful screening system for predicting drug interactions that can occur in a clinical situation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Role of P-glycoprotein in renal tubular secretion of digoxin in the isolated perfused rat kidney.

The mechanism for renal tubular secretion of digoxin as well as its interaction with quinidine or verapamil were investigated using the isolated perfused rat kidney. [3H]Digoxin was instantaneously administered into the renal artery together with [14C]inulin and Evans blue-albumin, and renal venous and urinary outflow curves were measured. The ratio of fractional excretion to filtration fraction for digoxin was 2.40 +/- 0.40, indicating involvement of tubular secretion. Quinidine and verapamil decreased the ratio of fractional excretion to filtration fraction in a concentration-dependent manner, and this inhibition was indicated to occur at transport from cells to lumen across luminal membranes. Neither tetraethylammonium nor p-aminohippurate affected the renal handling of digoxin. Because ouabain and digitoxose showed no influence on the value of fractional excretion to filtration fractions, Na+,K(+)-ATPase is not involved in the tubular secretion of digoxin. A metabolic inhibitor, 2,4-dinitrophenol, markedly inhibited digoxin secretion. Agents that bind to P-glycoprotein, such as vinblastine, daunorubicin and reserpine, markedly inhibited the secretion of digoxin. Recently, we have found that digoxin is a substrate transported by P-glycoprotein. The findings obtained here support the hypothesis that digoxin is secreted by P-glycoprotein located on the luminal membrane of renal tubular epithelial cells, and that clinically important interactions with quinidine and verapamil are caused by the inhibition of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Inositol phosphate-diacylglycerol signaling pathway in regulation of intraocular pressure.

To clarify the role of the inositol phosphate diacylglycerol (PI) signaling pathway in the regulation of intraocular pressure (IOP), we examined the effects of the tumor promoter phorbol ester (PMA) and Ca ionophore A23187 on IOP responses in albino rabbits. It was known that PMA stimulates protein kinase C (PKC) directly and that A23187 elevates intracellular Ca2+ concentration. In this study, the topical application of 10 microM PMA or 15 microM A23187 slightly reduced IOP. However, when both 10 microM PMA and 15 microM A23187 were topically applied the IOP was significantly reduced between 2 and 10 hours after A23187 application. The maximum IOP decrease was 5.0 mmHg at 3 hours. This decrease was inhibited by pretreatment with 0.5 microM staurosporin, a PKC inhibitor. These findings suggest that the PI signaling pathway somehow mediates aqueous dynamic changes in the eye.

Alkaloids↗